Recent studies from several different laboratories have provided further insight into structure-function relationships of cyclic nucleotide-gated channel and in particular the cCMPgated channel of rod photoreceptors. Site-directed mutagenesis and rod-olfactory chimeria constructs have defined important amino acids and peptide segments of the channel that are important in ion blockage, ligand specificity, and gating properties. Molecular cloning studies have indicated that cyclic nucleotide-gated channels consist of two subunits that are required to reproduce the properties of the native channels. Biochemical analysis of (...) the cGMP-gated channel of rodcells have indicated that the 240 kDa protein that co-purifies with the 63 kDa channel subunit contains both the previously cloned second subunit of the channel and a glutamic acid-rich protein. The regulatory properties of the cGMP-gated channel from rod cells has also been studied in more detail. Studies indicate that the beta subunit of the cGMP-gated channel of rod cells contains the binding site for calmodulin. Interaction of calmodulin with the channel alters the apparent affinity of the channel for cGMP in all in vitro systems that have been studied. The significance of these recent studies are discussed in relation to the commentaries on the target article. (shrink)

The cyclic GMP-gated channel responds to changes in free intracellular cGMP, and as a result, it plays a central role in the phototransduction process in rod and cone photoreceptor cells. Recent biochemical, immunochemical, and molecular biology studies indicate that this channel consists of a complex of two distinct subunits and one or more associated proteins. Primary structural analysis indicates that the a and (3 subunits contain a cGMP-binding domain, an even number of membrane-spanning segments, a voltage sensor motif and a (...) pore region. The latter two features are found in voltage-gated channels and suggest that these two classes of channels have evolved from the same ancestral channel protein. A working model for the membrane topography of the channel subunits is proposed based on immunogold labeling studies and sequence analysis. Recent studies also indicate that calmodulin binds to the 240 kDa protein of the channel complex and modulates the sensitivity of the channel for cGMP in a Ca2+-dependent manner. The molecular properties of the channel complex and the possible role of Ca2+-calmodulin modulation of the channel during photoactivation and photorecovery are discussed in relation to the current mechanism of phototransduction in photoreceptor cells. (shrink)

In International Law and World Order, B. S. Chimni articulates an integrated Marxist approach to international law combining the insights of Marxism, socialist feminism and postcolonial theory. The book uses IMAIL to systematically and critically examine the most influential contemporary theories of international law including new, feminist, realist and policy-oriented approaches. In doing so, it discusses a range of themes relating to the history, structure and process of international law. The book also considers crucial world order issues and problems that (...) the international legal process has to contend with, including the welfare of weak groups and nations, the ecological crisis and the role of human rights. This extensively revised second edition provides an invaluable, in-depth and updated review of the key literature and scholarship within this field of study. It will be of particular interest to students and scholars of international law, international relations, international politics and global studies. (shrink)

This paper investigates a well-known case of simultaneous discovery in twentieth-century chemistry, the origins of the concept of hybridisation, in the light of Kuhn's insights. There has been no ambiguity as to who discovered this concept, when it was "rst in print, and how important it was. The full-#edged form of the concept was published in 1931 independently by two American scientists John C. Slater (1900}1976) and Linus Pauling (1901}1994), although both of them had made their ideas public earlier: Slater (...) at the American Physical Society meetings in 1930, and Pauling in the Proceedings of the National Academy of Sciences in 1928. Slater and Pauling both argued for the necessity of using an s orbital as well as three p orbitals in the carbon atom in order to explain carbon's four valences and the tetrahedral structure of methane. The metaphor &hybridisation' for denoting this mix of s and p orbitals was "rst used by Robert S. Mulliken and J. H. Van Vleck before gaining currency with the scienti"c community around 1935.2 The concept of hybridisation was indeed indispensable for extending the quantum-mechanical interpretation of the chemical bond as an electron pairing from diatomic molecules to polyatomic ones. To be sure, the emergence of hybridisation attests to scientists' growing interest in exploring the borderland between physics and chemistry, a trend that led to the creation of physical chemistry in the late nineteenth century and of chemical physics and quantum chemistry in the 1920s and 30s. Slater and Pauling themselves experienced and on many occasions talked about the fruitfulness of interdisciplinary research; and historians have legitimately illuminated their works by examining them in this broad context.3 Yet the careful analysis of their research notes and published papers reveals that Slater and Pauling were working in quite disparate disciplinary traditions, with di!erent approaches, for di!erent audiences, and towards di!erent goals. The aim of this paper is to explore their di!erent routes to a common destination*hybridisation*and thereby to explicate tensions existing between physics and chemistry amidst the institutional and conceptual overlapping of the two disciplines. (shrink)

Drawing from the Boulding''s (1956) framework for general systems theory, the need to employ richer paradigm in the study of organizations (Pondy and Mitroff, 1979) is reiterated. It is argued that a better understanding of organizational ethical behavior is contingent upon viewing organizations as symbol processing systems of shared language and meanings. Further, it is proposed that organizations, like individuals, develop into collectivities of shared cognitions and rationale, over a period of time. The study adapts Kohlberg''s (1983) model of moral (...) development to examine if organizations can be viewed as passing through different stages of moral development depending on the type of moral reasoning employed to explain their behaviors in the face of ethical crises. Several cases raising questions about the ethics of corporate behavior were researched. An instrument entitled Organization Response Analysis was constructed using statements made by various spokespersons representing five of these organizations. The instrument was administered to 246 graduate and undergraduate students of business (N = 246). Results indicated a great degree of concurrence among respondents of differing genders, levels of education and work experience in determining the stages of moral development of organizations. Limitations of the current study and implications for future research and practice are discussed. (shrink)

In his account of probable reasoning, Poincaré used the concept, or at least the language, of conventions. In particular, he claimed that the prior probabilities essential for inverse probable reasoning are determined conventionally. This paper investigates, in the light of Poincaré's well known claim about the conventionality of metric geometry, what this could mean, and how it is related to other views about the determination of prior probabilities. Particular attention is paid to the similarities and differences between Poincaré's conventionalism as (...) it applies to probabilities and de Finetti's subjectivism. The aim of the paper is to suggest that in accounts of the development of ideas about probable reasoning, particularly those customarily described as Bayesian, Poincaré's discussion deserves more attention than it has so far received. (shrink)

In his account of probable reasoning, Poincare used the concept, or at least the language, of conventions. In particular, he claimed that the prior probabilities essential for inverse probable reasoning are determined conventionally. This paper investigates, in the light of Poincare's well known claim about the conventionality of metric geometry, what this could mean, and how it is related to other views about the determination of prior probabilities. Particular attention is paid to the similarities and differences between Poincare's conventionalism as (...) it applies to probabilities and de Finetti's subjectivism. The aim of the paper is to suggest that in accounts of the development of ideas about probable reasoning, particularly those customarily described as Bayesian, Poincare's discussion deserves more attention than it has so far received. (shrink)

Simultaneous discovery in science has been a subject of close historical investigations, not only for assessing claims of priority, which occasionally generate controversy rather than consensus, but also for understanding the cultural and intellectual context of the time. Thomas S. Kuhn is a pioneer in the contextual study of simultaneous discovery, and his paper on the formulation of the first law of thermodynamics has already become a classic.

This paper addresses whether universal, general education programs are enough to satisfy basic criteria of human rights, or whether comprehensive family planning programs, in conjunction with universal education programs, might also be morally required. Even before the Reagan administration instituted the ‘global gag rule’ at the 1984 conference in Mexico City, prohibiting funding to nongovernmental organizations that included providing information about abortion as a possible method of family planning, the moral acceptability of family planning programs has been called into question. (...) This paper makes a moral argument for family planning by appealing to both data and to theory: data about the efficacy of universal and comprehensive family planning education programs at reducing fertility and infant mortality, and theory about what is required for the establishment of autonomy. It reasons that universal educational programs are insufficient for the promotion of autonomy, and therefore argues on substantive autonomy grounds for comprehensive family planning programs in addition to universal education programs. (shrink)